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nmda

N-methyl-D-aspartate (NMDA) and NMDA receptors (NMDAR)

see also:

Introduction

  • NMDA is an amino acid derivative that acts as a specific agonist at the NMDA receptor mimicking the action of glutamate, the neurotransmitter which normally acts at that receptor
  • unlike glutamate, NMDA only binds to and regulates the NMDA receptor and has no effect on other glutamate receptors (such as those for AMPA and kainate)
  • NMDA receptors are thought to mediate alcohol withdrawal symptoms such as agitation and perhaps seizure
  • at homeostatic levels NMDA plays an essential role as a neurotransmitter and neuroendocrine regulator

N-methyl-D-aspartate receptors (NMDAR)

  • agonist binding to its NR2 subunits results in a non-specific cation channel opening, which can allow the passage of Ca2+ and Na+ into the cell and K+ out of the cell
  • will only open if glutamate is in the synapse and concurrently the postsynaptic membrane is already depolarized - acting as coincidence detectors at the neuronal level
  • the excitatory postsynaptic potential (EPSP) produced by activation of an NMDA receptor also increases the concentration of Ca2+ in the cell.

GluN2B-containing NMDARs

  • this receptor is critical for promoting physiological synaptic plasticity and neuronal viability.1)

NMDAR antagonists

    • GluN2B-containing NMDARs appear to be the main action of ketamine 2)
  • amantadine
  • dextromethorphan (DXM)

Anti-NMDA receptor encephalitis

  • an autoimmune condition, with the primary target of antibodies being the GluN1 subunit of the N-methyl-D-aspartate receptors (NMDAR) in the brain
  • rare: one in 1.5 million people per year but is is relatively common compared to other paraneoplastic disorders.
  • 80% are female
  • can occur at any age but most commonly under age 45yrs
  • 1st described in 2007
  • aetiology
    • tumours
      • half of cases are associated with tumors, most commonly teratomas of the ovaries
      • accounts for ~half the cases in children
    • other causes
  • clinical features
    • fever, headache, malaise, flu-like illness initially which may precede onset of encephalitis features by days or weeks
    • often followed by delusions and hallucinations with agitation and confusion
    • may then develop seizures or motor disturbances (“piano playing”, “pedalling”), and some develop catatonia
    • 4% mortality rate
    • 10% recurrence rate
  • Dx
    • NMDA receptor antibodies can be detected in serum and/or CSF
  • Rx
    • remove cause if possible
    • immunosuppression
nmda.txt · Last modified: 2025/02/16 22:45 by gary1

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